One of the most difficult problems in in vivo imaging of living organisms is how to distinguish between normal and aberrant tissue. Many approaches to this problem have been developed, including inter alia, X-ray imaging (including CAT-scanning), radionuclide imaging, fluoroscopy, ultrasonic imaging and nuclear magnetic resonance (NMR) imaging (MRI), with and without the administration of imaging agents, e.g., contrast media. The imaging agent may comprise materials which are themselves opaque to the detection signal and simply increase the contrast between organs or tissues containing it and organs or tissues which do not, e.g., as with X-ray agents. Alternatively, the agent can be one which has a local effect on the endogenous moiety active to the modality, as in the effect of NMR contrast agents on protons in vivo. For example, such agents may comprise materials which are selectively biodistributed due to pharmacokinetics or affinity for a certain compound, cell type, tissue, organ etc. In the latter case, the agent will highlight those areas containing the matter for which the agent has affinity; in the former, it will highlight the areas where it is selectively transported. Many such imaging agents are well known in the relevant arts, as are methods of use thereof.
Each of the known agents and methods suffers from a variety of deficiencies related to tolerability of the imaging agent, invasive nature of the active radiation and efficiency and accuracy of the diagnosis enabled by the resulting image.
Under many circumstances each modality provides very detailed information by imaging of various tissues. However, each suffers from a limitation based upon the lack of distinction between normal and aberrant tissue which has the same imaging modality signature. Although several approaches have been taken toward increasing the specificity of contrast agents (often in combination with targeting agents, e.g., antibodies), and thus expanding the applicability of a given modality, these are limited in that they rely on administration of materials, e.g., antibodies, whose in vivo specificity is essentially unalterable. The known contrast agents, such as, e.g., gadolinium-DTPA for MRI, are not universally specific for all abnormal vs. normal tissue. What is needed are contrast agents for each modality which are specific for a wider variety of aberrant tissue versus its normal tissue counterpart, to provide overall applicability as universally as possible, and which can correspondingly be used to locate and diagnose aberrant tissues in a large proportion of the body of a living organism.